(S,Z)-N-(1-bromo-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-1-(4-hydroxyphenyl)-3-oxoprop-1-en-2-yl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S,Z)-N-(1-bromo-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-1-(4-hydroxyphenyl)-3-oxoprop-1-en-2-yl)benzamide
• 英文别名: N-[(Z)-1-bromo-1-(4-hydroxyphenyl)-3-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-3-oxoprop-1-en-2-yl]benzamide
• 化学式: C₂₅H₂₃BrN₂O₄
• 分子量: 495.373
• InChiKey: DWNNDLYZTBJRFI-LPNGOHTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  98.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S,Z)-N-(1-bromo-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-1-(4-hydroxyphenyl)-3-oxoprop-1-en-2-yl)benzamide 、 二甲氨基氯乙烷盐酸 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以13.6%的产率得到(S,Z)-N-(1-bromo-1-(4-(2-(dimethylamino)ethoxy)phenyl)-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-3-oxoprop-1-en-2-yl)benzamide
  参考文献：
  名称：

  Design, synthesis and evaluation of novel phenyl propionamide derivatives as non-nucleoside hepatitis B virus inhibitors

  摘要：

  As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC50 values on HBV DNA replication of 0.46 and 0.14 mu M, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153.14, suggesting that 8d and 9b exhibited favorable safety profiles. Interestingly, 8d and 9b possessed significantly antiviral activities against lamivudine and entecavir resistant HBV mutants with IC50 values of 0.77 and 0.32 mu M. Notably, preliminary anti-HBV action mechanism studies showed that 8d could inhibit intracellular HBV pgRNA and RT activity of the HBV polymerase. Molecular docking studies suggested that compound 8d could fit into the dimer-dimer interface of HBV core protein by hydrophobic interaction. In addition, in silico prediction of physicochemical properties showed that 8d conformed well to the Lipinski's rule of five, suggesting its potential for use as a drug like molecule. Taken together, 8d possessed significantly anti-HBV activity, low toxicity, diverse anti-HBV mechanism and favorable physicochemical properties, and warranted further investigation as a promising non-nucleoside anti-HBV candidate. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.042
• 作为产物：
  描述：

  (S,E)-N-(3-((1-hydroxy-3-phenylpropan-2-yl)amino)-1-(4-hydroxyphenyl)-3-oxoprop-1-en-2-yl)benzamide 在 溴 、 calcium carbonate 作用下， 以 氯仿 为溶剂， 以18%的产率得到(S,Z)-N-(1-bromo-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-1-(4-hydroxyphenyl)-3-oxoprop-1-en-2-yl)benzamide
  参考文献：
  名称：

  Design, synthesis and evaluation of novel phenyl propionamide derivatives as non-nucleoside hepatitis B virus inhibitors

  摘要：

  As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC50 values on HBV DNA replication of 0.46 and 0.14 mu M, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153.14, suggesting that 8d and 9b exhibited favorable safety profiles. Interestingly, 8d and 9b possessed significantly antiviral activities against lamivudine and entecavir resistant HBV mutants with IC50 values of 0.77 and 0.32 mu M. Notably, preliminary anti-HBV action mechanism studies showed that 8d could inhibit intracellular HBV pgRNA and RT activity of the HBV polymerase. Molecular docking studies suggested that compound 8d could fit into the dimer-dimer interface of HBV core protein by hydrophobic interaction. In addition, in silico prediction of physicochemical properties showed that 8d conformed well to the Lipinski's rule of five, suggesting its potential for use as a drug like molecule. Taken together, 8d possessed significantly anti-HBV activity, low toxicity, diverse anti-HBV mechanism and favorable physicochemical properties, and warranted further investigation as a promising non-nucleoside anti-HBV candidate. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.042